A significant hurdle in tissue engineering is adequate perfusion of donor tissue. Since the diffusion limit of oxygen is <200um (Carmeliet and Jain, 2000), even fairly simple tissue constructs require rapid perfusion following transplantation. Thus, successfully engineered tissues are restricted to thin or a vascular tissues such as skin, cartilage, bladder etc (Rouwkema et al., 2008). Interestingly, a related problem plagues therapeutic angiogenesis approaches to treat ischemic disease. Despite the discovery of numerous pro-angiogenic factors, clinical therapeutic strategies based on single factors have been wholly unsuccessful (Henry et al., 2003;Molin and Post, 2007;Simons, 2005);however, combinations of growth factors are beginning to show great promise in promoting stable angiogenesis and improving damaged circulation, inspiring new designs of pro-angiogenic tissue scaffolds. Here we will use multiple transgenic fluorescent reporter lines in a novel strategy to optimize hydrogel scaffolds for tissue engineering and for use in treating ischemic disease. Research goals include the optimization of hydrogel scaffold design to deliver growth factors and cells and the characterization of the host response to guide new scaffold designs. PUBLIC HEALTH RELEVANCE: Current strategies to repair damaged tissues are limited by the lack of efficient methods to improve circulation and rebuild tissues in damaged areas. In this proposal we will design and test whether custom engineered scaffolds can aid in vessel infiltration and can deliver donor cells that can participate in repair.